The "activated" lymphocyte appears to be the central effector in cell mediated immunologic reactions resulting in the tissue destruction observed in transplantation immunity, neoplasia, delayed hypersensitivity, and certain autoimmune diseases. Yet the cell and molecular mechanisms involved in these important reactions are just beginning to be defined, primarily due to the recent advent of in vitro systems, felt to be experimental models of the in vivo situation(s). The in vitro systems permit basic studies and avoid the complexity of the milieu interieur. "Activated" lymphocytes also secrete a family of soluble effector molecules, one of which is a cell toxin, termed lymphotoxin (LT), which may be an important effector of cell destruction in these cytotoxic reactions. The present studies will employ modern in vitro and biochemical techniques to examine the relationship of the cell and molecular events occurring when human and murine lymphocytes become activated to become cytotoxic effector cells, and the relationship of activation and effector molecule secretion in these events. These studies center around the following main topics: A. Morphologic and biochemical studies of how human lymphotoxin induces cell destruction in vitro. B. Physical and chemical characterization of representative human lymphokine molecules. C. Control mechanism(s) regulating lymphocyte activation itself, and the secretion of LT and of other representative LK by antigen and mitogen activated human lymphocytes. D. Biochemical and morphologic studies on the actual role of LT as a major effector of human and murine lymphocyte-induced cytolytic reactions in vitro and in vivo.